Evidence map›Paper›PMID 42870374›Full record

ArticleCancer medicine2026

Impact of p53 Target Genes on Drug Resistance in TP53-Mutated B-Cell Precursor Acute Lymphoblastic Leukemia.

Thao T T Nguyen, Minori Tamai, Koshi Akahane, Chiaki Komatsu, Keiko Kagami, Xuekang Qi, Luay Aswad, Kunio Miyake, Shin Kasai, Shinpei Somazu and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Thao T T NguyenDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.
Minori TamaiDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.ORCID https://orcid.org/0000-0001-6905-4582
Koshi AkahaneDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.ORCID https://orcid.org/0000-0001-8591-1281
Chiaki KomatsuDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.
Keiko KagamiDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.
Xuekang QiClinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.ORCID https://orcid.org/0000-0002-2659-309X
Luay AswadClinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.
Kunio MiyakeDepartment of Epidemiology and Environmental Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Japan.ORCID https://orcid.org/0000-0001-9196-2229
Shin KasaiDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.ORCID https://orcid.org/0009-0003-2708-9906
Shinpei SomazuDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.ORCID https://orcid.org/0000-0001-5153-4545
Atsushi WatanabeDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.ORCID https://orcid.org/0000-0002-4181-8111
Kumiko GoiDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.
Koichi OshimaInstitute for Cancer Genetics, Columbia University, New York, New York, USA.ORCID https://orcid.org/0000-0002-0771-3551
Hiroshi ImanagaDepartment of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.ORCID https://orcid.org/0000-0003-1012-2311
Yuichiro SembaDivision of Precision Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.ORCID https://orcid.org/0000-0001-8576-3530
Masashi SanadaDepartment of Advanced Diagnosis, Clinical Research Center, NHO Nagoya Medical Center, Nagoya, Japan.
Janne LehtiöClinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.
Hiroaki GotoDivision of Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Japan.ORCID https://orcid.org/0000-0001-6737-1509
Masayoshi MinegishiJapanese Red Cross Miyagi Blood Center, Sendai, Japan.
Toshiya InabaDepartment of Animal Experimentation, The Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan.
Shotaro IwamotoDepartment of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
Takahiro MaedaDivision of Precision Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.ORCID https://orcid.org/0000-0003-4530-6460
Rozbeh JafariClinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.ORCID https://orcid.org/0000-0002-3396-4709
Takeshi InukaiDepartment of Pediatrics, School of Medicine, University of Yamanashi, Chuo, Japan.ORCID https://orcid.org/0000-0002-4783-2184

Funding

Japan Society for the Promotion of Science 19K08833Japan Society for the Promotion of Science KAKENHI 23K24298The Japanese Society of Hematology Research FY2022
6 · The paper itself

Abstract

TP53 mutations are linked to poor prognoses in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), indicating that specific p53 target genes may contribute to drug resistance. Although the impact of specific genetic alterations on drug sensitivity has been reported in BCP-ALL, the effects of TP53 mutations on sensitivity to individual agents remain poorly defined in the clinical setting because of the use of combination chemotherapy regimens. In the present study, we addressed this issue through two complementary analyses using a large panel of BCP-ALL cell lines. Initially, 30 cell lines harboring TP53 mutations demonstrated significantly greater resistance to daunorubicin (DNR), mafosfamide (MAF; an active analog of cyclophosphamide), 6-mercaptopurine (6-MP), and prednisolone compared to 46 cell lines without mutations. Second, 11 CRISPR/Cas9-mediated TP53-knockout sublines derived from cell lines with wild-type TP53 recapitulated resistance to DNR, MAF, and 6-MP, as well as to vincristine (VCR) and cytarabine (Ara-C). Consistent with these findings, re-evaluation of genome-wide CRISPR screening datasets revealed significant enrichment of TP53 gRNAs in cells treated with DNR, MAF, 6-MP, Ara-C, and VCR. Furthermore, transcriptomic and proteomic analyses of p53 target genes in the two cell line models, along with re-evaluation of genome-wide CRISPR screening datasets, identified BAX, BBC3, and FDXR as key p53 target genes associated with multidrug resistance. These results highlight the potential value of targeting these p53 downstream pathways to improve outcomes in TP53-mutated BCP-ALL cases.

Indexed as

Drug Resistance, NeoplasmMutationPrecursor B-Cell Lymphoblastic Leukemia-LymphomaTumor Suppressor Protein p53Cell Line, TumorDaunorubicinHumansMercaptopurineVincristineDaunorubicinMercaptopurineTP53 protein, humanTumor Suppressor Protein p53VincristineB‐cell precursor acute lymphoblastic leukemiacell linedrug resistancep53 target genesTP53 mutation

Identifiers

PMID42870374
PMCPMC13662230

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.